Safety, Pharmacokinetics, and Pharmacodynamics of MK-8876 in Participants With Hepatitis C Infection (MK-8876-003)

NCT01930058 | Completed Phase 1 Results

• 2 other identifiers: 8876-0032013-002566-39
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

Brief Summary

This adaptive design study will evaluate the safety, pharmacokinetics, and effect on hepatitis C virus (HCV) RNA levels of multiple doses of MK-8876 in participants with HCV infection. The study will consist of 4 parts evaluating participants infected with specific hepatitis C virus genotypes and up to 10 panels allowing for additional participants to enroll in each panel as specified in the study analysis. The hypothesis evaluated in the study is that a ≥2.5 log IU/mL reduction in HCV RNA from Baseline will accompany multiple dose administration of MK-8876 in participants with HCV infection.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in HCV Viral Load

  The mean change (log10) in HCV ribonucleic acid (RNA) from baseline to Day 7 was determined for each panel of participants.

  Baseline and Day 7

Secondary Outcomes (5)

• Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (hr) Post-dose (AUC0-24 hr) of MK-8876

  Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

• Maximum Plasma Concentration (Cmax) of MK-8876

  Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

• Trough Plasma Concentration (C24hr) of MK-8876

  24 hours post-dose on Days 1 and 7

• Time to Maximum Plasma Concentration (Tmax) of MK-8876

  Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

• Apparent Terminal Plasma Half-life (t½) of MK-8876

  Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Day 7

Study Arms (3)

Panel A: HCV GT3 MK-8876 150 mg

EXPERIMENTAL

Participants infected with HCV GT3 received 150 mg MK-8876 once daily (q.d.) by mouth for 7 days.

Drug: MK-8876

Panel B: HCV GT3 MK-8876 800 mg

EXPERIMENTAL

Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.

Drug: MK-8876

Panel E: HCV GT1a MK-8876 800 mg

EXPERIMENTAL

Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.

Drug: MK-8876

Interventions

MK-8876 DRUG

MK-8876 10 mg or 100 mg tablets taken q.d. by mouth.

Panel A: HCV GT3 MK-8876 150 mg; Panel B: HCV GT3 MK-8876 800 mg; Panel E: HCV GT1a MK-8876 800 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• is male, or female of non-childbearing potential (non-childbearing potential is defined as postmenopausal without menses for ≥1 year or after medically documented hysterectomy, oophorectomy, or tubal ligation)
• agrees to use a medically acceptable method of contraception through 90 days after the last dose of study drug if participant has a female partner of childbearing potential must (males should use a condom and their partner of childbearing potential must use hormonal contraception, intrauterine device, diaphragm, cervical cap, or female condom)
• has a body mass index (BMI) between 18 and 37 kg/m\^2
• has a clinical diagnosis of chronic HCV infection defined by positive serology for HCV for ≥6 months
• agrees to follow the smoking and other trial restrictions

You may not qualify if:

• is mentally or legally institutionalized or incapacitated, has significant emotional problems at study start or has clinically significant psychiatric disorder of the last 5 years
• has a history of clinically significant endocrine, gastrointestinal (except HCV infection), cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• has a history of stroke, chronic seizures, or major neurological disorder
• has a history of cancer (except adequately treated non-melanomatous skin carcinoma, carcinoma in situ of the cervix, or other malignancies which have been successfully treated for ≥10 years
• has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to drugs or food
• has a history of clinically significant hepatic disease, Gilbert's disease, biliary tract disease, or human immunodeficiency virus
• has had major surgery or donated or lost \>1 unit of blood within 4 weeks before the study
• has participated in another investigational trial within 4 weeks before the study
• Is unable to refrain from or anticipates the use of any medication from 2 weeks before the study and throughout the study
• consumes \>2 glasses of alcoholic beverages per day
• consumes \>6 servings (1 serving is \~120 mg caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day
• is a regular user of any illicit drugs or history of drug abuse within 12 months of the study
• has evidence or history of chronic hepatitis not caused by HCV (except acute non-HCV-related hepatitis that resolved \>6 months before the study)
• has previously received treatment with another HCV non-nucleoside inhibitor (previous use of other HCV investigational therapies or marketed compounds is permitted if treatment ended ≥3 months before the study)
• has clinical or laboratory evidence of advanced or decompensated liver disease

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2013
• First Posted: August 28, 2013
• Study Start: October 2, 2013
• Primary Completion: May 5, 2014
• Study Completion: May 5, 2014
• Last Updated: October 25, 2018
• Results First Posted: February 4, 2016

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share